Figure 1. Possible Outcomes for Anticancer Agents Administered as Combinations.

In this illustration, ten patients with cancer receive treatment with drugs A, B, and C. If drugs A and B are administered sequentially, the patient symbol shown in teal blue represents an objective clinical response to A. If the entire group is subsequently treated with B, three additional patients (shown in lavender) respond to B. Under the independent action model, the response of a patient to the combination of A + B is the best response to either A or B. In this example, all responses are assumed to be partial. If drugs A and B are delivered concurrently, the response of the tumor sensitive to either/both A and B is also partial and occurs in the same number of patients, since drug action does not combine to give a better response rate. However, under certain more limited clinical circumstances, sometimes based on known or hypothesized interactions between specific molecular pathways, drugs can be chosen (B + C) that produce complementary therapeutic effects, with acceptable toxicity, that encompass not only the independent actions of drugs B (lavender) and C (orange), but also engagement of novel mechanisms of growth control (patients in both lavender and orange), leading to greater therapeutic activity.

Adapted from Sartorelli (Sartorelli, 1969).